title: Telmisartan attenuates oxidative stress and renal fibrosis in streptozotocin induced diabetic mice with the alteration of angiotensin-(1-7) mas receptor expression associated with its PPAR-γ agonist action.
abstract: The beneficial effects of telmisartan on Angiotensin (Ang)-II mediated oxidative stress and renal fibrosis in streptozotocin (STZ)-induced diabetic nephropathy (DN) were studied. Thirty mice were divided into normal (NG), STZ-induced diabetic (DG) and telmisartan-treated diabetic (TG) groups. Compared with NG mice, DG mice showed significant up-regulations of AT-1R, TGF-β1, p-p38MAPK, p-MAPKAPK-2, p-Akt, p47phox, p67phox, gp91phox protein and collagen-III and all of these were significantly reversed in TG mice. The down-regulated protein expression of Ang-(1-7) mas receptor, ACE-2, PPAR-γ and PGC-1α were observed in DG mice and a significant up-regulation effect of telmisartan has been seen in the TG mice. Furthermore, TG mice showed reduced expression of fibronectin, production of superoxide radical as well as renal hypertrophy and fibrosis when compared with DG mice. These findings suggest that Ang-II plays a significant role in DN and telmisartan would be beneficial in reducing oxidative stress and fibrosis in STZ-induced DN.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Arun Prasath
authors.initials: AP
authors.lastname: Lakshmanan
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Rajarajan A
authors.initials: RA
authors.lastname: Thandavarayan
authors.forename: Flori R
authors.initials: FR
authors.lastname: Sari
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.forename: Vijayasree V
authors.initials: VV
authors.lastname: Giridharan
authors.forename: Vivian
authors.initials: V
authors.lastname: Soetikno
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D024061:Collagen Type III / Q000187:drug effects / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy*; D005355:Fibrosis; D006984:Hypertrophy / Q000150:complications / Q000188:drug therapy; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D047495:PPAR gamma / Q000819:agonists*; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000187:drug effects / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000804:Angiotensin II; D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D024061:Collagen Type III; D047908:Intracellular Signaling Peptides and Proteins; D019255:NADPH Oxidases; D047495:PPAR gamma; D007703:Peptidyl-Dipeptidase A; D017346:Protein Serine-Threonine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D000077333:Telmisartan; D053773:Transforming Growth Factor beta1; D000099190:MAP-Kinase-Activated Kinase 2